Diseases within the human eye involving the retina, the vitreous, and their interaction at the vitreoretinal juncture (VRJ) are collectively a major cause of visual loss; these form a spectrum of lesions that may be spontaneous, secondary to ocular lesions, complications of systemic conditions, or unfortunately, an untoward reaction to ocular operations. Those found in the posterior fundus may involve the macula and include many proliferative lesions: simple epiretinal membrane (usually subtle and asymptomatic), surface wrinkling retinopathy (which may be accompanied by significant visual loss), and more complex nonvascular proliferative extraretinopathies (NPE) (which may culminate in irreversible retinal detachment and blindness). In the peripheral fundus, degenerative lesions of the retina interact with the vitreous or the zonule at the VRJ and may lead to retinal breaks and detachment; for reasons presently poorly understoon the treatment of these retinal detachments may be seriously limited by adverse interactions between the conditions in the periphery with those of the posterior fundus. This research project studies in man the gross, light microscopic and ultrastructural features of lesions of the VRJ to determine those factors that predispose the VRJ to both degenerative and proliferative lesions. As the background anatomical and the simpler pathological conditions have become clarified, we are broadening the investigation to include the more complex nonvascular extraretinopathies and then the extraretinal vascular lesions (as in diabetes mellitus). Because of work done by other laboratories identifying the role of the retinal pigment epithelium in some of the more complex NPE, we have recently expanded our interest to include studies of the chorioretinal juncture. Finally, we have another no-less-important goal, to clarify with ultrastructural studies the features of degenerative lesions of the peripheral fundus that promote adverse interaction with those of the posterior fundus. It is expected that information derived from this project will continue to yield information that will provide a better understanding of lesions of the VRJ and thereby improve the management of patients.